Hybrid resistance is the prevention of proliferation of grafts of H-2 homozygous normal or neoplastic hemopoietic cells by F1 hybrid mice heterozygous at H-2. This observation goes against the laws of transplantation genetics, which state that histocompatibility antigens are inherited codominantly. The determinants for the major hybrid or hemopoietic histocompatibility (Hh) antigens map at H-2D. The aims here are to determine if genes in the trans or cis configuration with Hh regulate expression so as to determine immunogenicity of donor cells and presence or absence of hybrid resistance in F1 hybrid hosts. The possibility of allogeneic inhibition, i.e., recognition of host alloantigens by the donor cells to initiate the response, will be investigated. Finally, the mechanism of tolerance induction to Hh antigens will be explored. The potential importance of this work relates to autoimmunity and tumor immune surveillance, since the parent and the F1 hybrid share the structural gene for the same Hh antigen. (SR)